A ten-gene DNA-damage response pathway gene expression signature predicts gemtuzumab ozogamicin response in pediatric AML patients treated on COGAAML0531 and AAML03P1 trials.


Journal

Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895

Informations de publication

Date de publication:
08 2022
Historique:
received: 06 12 2021
accepted: 27 05 2022
revised: 17 05 2022
pubmed: 11 6 2022
medline: 4 8 2022
entrez: 10 6 2022
Statut: ppublish

Résumé

Gemtuzumab ozogamicin (GO) is an anti-CD33 monoclonal antibody linked to calicheamicin, a DNA damaging agent, and is a well-established therapeutic for treating acute myeloid leukemia (AML). In this study, we used LASSO regression modeling to develop a 10-gene DNA damage response gene expression score (CalDDR-GEx10) predictive of clinical outcome in pediatric AML patients treated with treatment regimen containing GO from the AAML03P1 and AAML0531 trials (ADE + GO arm, N = 301). When treated with ADE + GO, patients with a high CalDDR-GEx10 score had lower complete remission rates (62.8% vs. 85.5%, P = 1.7 7 * 10

Identifiants

pubmed: 35688939
doi: 10.1038/s41375-022-01622-0
pii: 10.1038/s41375-022-01622-0
pmc: PMC9357169
mid: NIHMS1813919
doi:

Substances chimiques

Aminoglycosides 0
Antibodies, Monoclonal, Humanized 0
Antineoplastic Agents, Immunological 0
Calicheamicins 0
Sialic Acid Binding Ig-like Lectin 3 0
DNA 9007-49-2
Gemtuzumab 93NS566KF7

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

2022-2031

Subventions

Organisme : NCI NIH HHS
ID : R21 CA155524
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180886
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180899
Pays : United States

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

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Auteurs

Mohammed O Gbadamosi (MO)

Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.

Vivek M Shastri (VM)

Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.

Abdelrahman H Elsayed (AH)

Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.

Rhonda Ries (R)

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Oluwaseyi Olabige (O)

Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.

Nam H K Nguyen (NHK)

Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.

Angelica De Jesus (A)

Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.

Yi-Cheng Wang (YC)

COG Statistics and Data Center, Monrovia, CA, USA.

Alice Dang (A)

COG Statistics and Data Center, Monrovia, CA, USA.

Betsy A Hirsch (BA)

University of Minnesota, Minneapolis, MN, USA.

Todd A Alonzo (TA)

COG Statistics and Data Center, Monrovia, CA, USA.
Biostatistics Division, University of Southern California, Los Angeles, CA, USA.

Alan Gamis (A)

Department of Hematology-Oncology, Children's Mercy Hospitals and Clinics, Kansas City, MO, USA.

Soheil Meshinchi (S)

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Jatinder K Lamba (JK)

Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA. jlamba@cop.ufl.edu.
Center for Pharmacogenomics and Precision Medicine, University of Florida, Gainesville, FL, USA. jlamba@cop.ufl.edu.

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